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[PMID]:29433476
[Au] Autor:Wen L; Wen YC; Ke GJ; Sun SQ; Dong K; Wang L; Liao RF
[Ad] Endereço:Department of Ophthalmology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, China.
[Ti] Título:TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells.
[So] Source:BMC Ophthalmol;18(1):38, 2018 Feb 12.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ca entry plays an important role in modulating endothelial cell migration and tube formation. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a Ca -permeable channel that is widely expressed in endothelial cells. It has been reported that TRPV4 is expressed in HRCECs and regulates Ca entry. However, the function of TRPV4 in human retinal capillary endothelial cells (HRCECs) remains unknown. METHODS: In this study we used western blot and immunostaining assay to verify TRPV4 expression in HRCECs. And then we pretreated HRCECs with HC067047 and transfected with specific shRNA of TRPV4. The functional presence of TrpV4 was determined by using fluorescence, migration and tube formation assay in TrpV4 knockdown cells or control cells. RESULTS: Using western blot and immunostaining, we confirmed TRPV4 expression in HRCECs. Moreover, inhibition of TRPV4 using the specific inhibitor HC067047 and the knockdown of TRPV4 with shRNA significantly suppressed tube formation and migration by HRCECs. CONCLUSIONS: TRPV4 is essential for HRCEC migration and tube formation, and maybe a potential therapeutic target for retinal vascular diseases.
[Mh] Termos MeSH primário: Movimento Celular/fisiologia
Células Endoteliais/citologia
Células Endoteliais/metabolismo
Vasos Retinianos/fisiologia
Canais de Cátion TRPV/fisiologia
[Mh] Termos MeSH secundário: Western Blotting
Cálcio/metabolismo
Agonistas dos Canais de Cálcio/farmacologia
Bloqueadores dos Canais de Cálcio/farmacologia
Contagem de Células
Células Endoteliais/efeitos dos fármacos
Técnica Indireta de Fluorescência para Anticorpo
Células HEK293
Seres Humanos
Lentivirus/genética
RNA Interferente Pequeno/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Calcium Channel Blockers); 0 (RNA, Small Interfering); 0 (TRPV Cation Channels); 0 (TRPV4 protein, human); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180218
[Lr] Data última revisão:
180218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180214
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0697-2


  2 / 1874 MEDLINE  
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[PMID]:28953655
[Au] Autor:Lu C; Zuo K; Lu Y; Liang S; Huang X; Zeng C; Zhang J; An Y; Wang J
[Ad] Endereço:Department of National Clinical Research Center of Kidney Disease, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
[Ti] Título:Apolipoprotein A-1-related amyloidosis 2 case reports and review of the literature.
[So] Source:Medicine (Baltimore);96(39):e8148, 2017 Sep.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Apolipoprotein A-1 (ApoA-1)-related amyloidosis is characterized by the deposition of ApoA-1 in various organs and can be either hereditary or nonhereditary. It is rare and easily misdiagnosed. Renal involvement is common in hereditary ApoA-1 amyloidosis, but rare in the nonhereditary form. PATIENT CONCERNS: We reported two cases with ApoA-1 amyloidosis, a 64-year-old man suffering from nephrotic syndrome and a 40-year-old man with nephrotic syndrome and splenomegaly. Renal biopsies revealed glomerular, interstitial and vascular amyloid deposits and positive phospholipase A2 receptor staining in the glomerular capillary loop in case 1, and mesangial amyloid deposits in case 2. DIAGNOSES: After immunostaining failed to determine the specific amyloid protein, proteomic analysis of amyloid deposits by mass spectrometry was performed and demonstrated the ApoA-1 origin of the amyloid. Genetic testing revealed no mutation of the APOA1 gene in case 1 but a heterozygous mutation, Trp74Arg, in case 2. Case 1 was thus diagnosed as nonhereditary ApoA-1 associated renal amyloidosis with membranous nephropathy, and case 2 as hereditary ApoA-1 amyloidosis with multiorgan injuries (kidney and spleen) and a positive family history. INTERVENTIONS: Case 1 was treated with glucocorticoid combined with cyclosporine. Case 2 was treated with calcitriol and angiotensin converting enzyme inhibitors. OUTCOMES: Two cases were followed up for 5 months and 2 years, respectively; and case 1 was found to have attenuated proteinuria while case 2 had an elevation of cholestasis indices along with renal insufficiency. LESSONS: Proteomic analysis by mass spectrometry of the amyloid deposits combined with genetic analysis can provide accurate diagnosis of ApoA-1 amyloidosis. Besides, these 2 cases expand our knowledge of ApoA-1-related renal amyloidosis.
[Mh] Termos MeSH primário: Amiloidose Familiar
Amiloidose
Apolipoproteína A-I/metabolismo
Rim/patologia
Síndrome Nefrótica
Placa Amiloide
Esplenomegalia
[Mh] Termos MeSH secundário: Adulto
Amiloidose/diagnóstico
Amiloidose/metabolismo
Amiloidose/fisiopatologia
Amiloidose Familiar/diagnóstico
Amiloidose Familiar/metabolismo
Amiloidose Familiar/fisiopatologia
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem
Calcitriol/administração & dosagem
Agonistas dos Canais de Cálcio/administração & dosagem
Ciclosporina/administração & dosagem
Diagnóstico Diferencial
Inibidores Enzimáticos/administração & dosagem
Glucocorticoides/administração & dosagem
Seres Humanos
Imunossupressores/administração & dosagem
Masculino
Espectrometria de Massas/métodos
Conduta do Tratamento Medicamentoso
Meia-Idade
Síndrome Nefrótica/diagnóstico
Síndrome Nefrótica/etiologia
Seleção de Pacientes
Placa Amiloide/metabolismo
Placa Amiloide/patologia
Receptores da Fosfolipase A2/metabolismo
Esplenomegalia/diagnóstico
Esplenomegalia/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Apolipoprotein A-I); 0 (Calcium Channel Agonists); 0 (Enzyme Inhibitors); 0 (Glucocorticoids); 0 (Immunosuppressive Agents); 0 (Receptors, Phospholipase A2); 83HN0GTJ6D (Cyclosporine); FXC9231JVH (Calcitriol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008148


  3 / 1874 MEDLINE  
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[PMID]:28882644
[Au] Autor:Weon H; Kim TW; Youn DH
[Ad] Endereço:Department of Oral Physiology, BioCure Laboratory, School of Dentistry, Kyungpook National University, 2177 Dalgubeol Blvd, Jung-gu, Daegu 41940, Republic of Korea.
[Ti] Título:Postsynaptic N-type or P/Q-type calcium channels mediate long-term potentiation by group I metabotropic glutamate receptors in the trigeminal oralis.
[So] Source:Life Sci;188:110-117, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Both N-type and P/Q-type voltage-gated Ca channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs). MAIN METHODS: (S)-3,5-Dihydroxyphenylglycine (DHPG; 10µM for 5min), the group I mGluR agonist, was used to induce LTP of excitatory postsynaptic currents that were evoked in the Vo neurons by stimulating the trigeminal track. KEY FINDINGS: Weak blockade of the N-type or P/Q-type VGCCs by ω-conotoxin GVIA or ω-agatoxin IVA, respectively, which inhibited only 20-40% of Ca currents recorded in isolated trigeminal ganglion neurons but had no effect on the basal excitatory synaptic transmission, completely blocked the induction of LTP. In contrast, stronger blockade of the channels, which inhibited >50% of Ca currents and about 30% of basal synaptic transmission, resulted in the development of long-term depression (LTD), the long-lasting decrease of synaptic strength. Interestingly, the postsynaptic mechanism of DHPG-induced LTP, which was determined by paired-pulse ratio, disappeared when LTP was blocked, or LTD occurred, while a presynaptic mechanism still remained. SIGNIFICANCE: Our data suggest that postsynaptic N-type and P/Q-type VGCCs mediate the DHPG-induced LTP at the trigeminal afferent synapses in the Vo.
[Mh] Termos MeSH primário: Canais de Cálcio Tipo N/fisiologia
Canais de Cálcio Tipo P/fisiologia
Canais de Cálcio Tipo Q/fisiologia
Potenciação de Longa Duração/fisiologia
Receptores de Glutamato Metabotrópico/fisiologia
Núcleo Espinal do Trigêmeo/fisiologia
[Mh] Termos MeSH secundário: Agatoxinas/farmacologia
Animais
Agonistas dos Canais de Cálcio/farmacologia
Bloqueadores dos Canais de Cálcio
Cromonas/farmacologia
Feminino
Potenciação de Longa Duração/efeitos dos fármacos
Depressão Sináptica de Longo Prazo/efeitos dos fármacos
Depressão Sináptica de Longo Prazo/fisiologia
Masculino
Terminações Pré-Sinápticas/fisiologia
Ratos
Receptores de Glutamato Metabotrópico/agonistas
Potenciais Sinápticos/fisiologia
Transmissão Sináptica/efeitos dos fármacos
Núcleo Espinal do Trigêmeo/efeitos dos fármacos
ômega-Conotoxinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((S)-3,7-dihydroxychroman-4-one); 0 (Agatoxins); 0 (Calcium Channel Agonists); 0 (Calcium Channel Blockers); 0 (Calcium Channels, N-Type); 0 (Calcium Channels, P-Type); 0 (Calcium Channels, Q-Type); 0 (Chromones); 0 (Receptors, Metabotropic Glutamate); 0 (omega-Conotoxins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE


  4 / 1874 MEDLINE  
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[PMID]:28654695
[Au] Autor:Nam HY; Balaji Raghavendran HR; Pingguan-Murphy B; Abbas AA; Merican AM; Kamarul T
[Ad] Endereço:Tissue Engineering Group, Department of Orthopaedic Surgery (NOCERAL), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
[Ti] Título:Fate of tenogenic differentiation potential of human bone marrow stromal cells by uniaxial stretching affected by stretch-activated calcium channel agonist gadolinium.
[So] Source:PLoS One;12(6):e0178117, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 µM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications.
[Mh] Termos MeSH primário: Agonistas dos Canais de Cálcio/farmacologia
Diferenciação Celular/efeitos dos fármacos
Gadolínio/farmacologia
Células Mesenquimais Estromais/efeitos dos fármacos
Estresse Mecânico
[Mh] Termos MeSH secundário: Idoso
Apoptose/efeitos dos fármacos
Caderinas/metabolismo
Células Cultivadas
Colágeno/metabolismo
Matriz Extracelular/metabolismo
Fibronectinas/metabolismo
Seres Humanos
Mecanotransdução Celular/efeitos dos fármacos
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/metabolismo
Meia-Idade
Engenharia Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (Calcium Channel Agonists); 0 (Fibronectins); 9007-34-5 (Collagen); AU0V1LM3JT (Gadolinium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178117


  5 / 1874 MEDLINE  
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[PMID]:28584051
[Au] Autor:Mowrey DD; Xu L; Mei Y; Pasek DA; Meissner G; Dokholyan NV
[Ad] Endereço:From the Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7260.
[Ti] Título:Ion-pulling simulations provide insights into the mechanisms of channel opening of the skeletal muscle ryanodine receptor.
[So] Source:J Biol Chem;292(31):12947-12958, 2017 Aug 04.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The type 1 ryanodine receptor (RyR1) mediates Ca release from the sarcoplasmic reticulum to initiate skeletal muscle contraction and is associated with muscle diseases, malignant hyperthermia, and central core disease. To better understand RyR1 channel function, we investigated the molecular mechanisms of channel gating and ion permeation. An adequate model of channel gating requires accurate, high-resolution models of both open and closed states of the channel. To this end, we generated an open-channel RyR1 model using molecular simulations to pull Ca through the pore constriction site of a closed-channel RyR1 structure determined at 3.8-Šresolution. Importantly, we find that our open-channel model is consistent with the RyR1 and cardiac RyR (RyR2) open-channel structures reported while this paper was in preparation. Both our model and the published structures show similar rotation of the upper portion of the pore-lining S6 helix away from the 4-fold channel axis and twisting of Ile-4937 at the channel constriction site out of the channel pore. These motions result in a minimum open-channel pore radius of ∼3 Šformed by Gln-4933, rather than Ile-4937 in the closed-channel structure. We also present functional support for our model by mutations around the closed- and open-channel constriction sites (Gln-4933 and Ile-4937). Our results indicate that use of ion-pulling simulations produces a RyR1 open-channel model, which can provide insights into the mechanisms of channel opening complementing those from the structural data.
[Mh] Termos MeSH primário: Sinalização do Cálcio
Bicamadas Lipídicas/química
Modelos Moleculares
Canal de Liberação de Cálcio do Receptor de Rianodina/química
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Cafeína/química
Cafeína/metabolismo
Cafeína/farmacologia
Agonistas dos Canais de Cálcio/química
Agonistas dos Canais de Cálcio/metabolismo
Agonistas dos Canais de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Glutamina/química
Células HEK293
Seres Humanos
Isoleucina/química
Ligantes
Simulação de Dinâmica Molecular
Mutação
Fragmentos de Peptídeos/agonistas
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica em alfa-Hélice
Domínios e Motivos de Interação entre Proteínas
Coelhos
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Rianodina/química
Rianodina/metabolismo
Rianodina/farmacologia
Canal de Liberação de Cálcio do Receptor de Rianodina/genética
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Ligands); 0 (Lipid Bilayers); 0 (Peptide Fragments); 0 (Recombinant Proteins); 0 (Ryanodine Receptor Calcium Release Channel); 04Y7590D77 (Isoleucine); 0RH81L854J (Glutamine); 15662-33-6 (Ryanodine); 3G6A5W338E (Caffeine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.760199


  6 / 1874 MEDLINE  
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[PMID]:28538150
[Au] Autor:Sárközi S; Komáromi I; Jóna I; Almássy J
[Ad] Endereço:Department of Physiology, Faculty of Medicine, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
[Ti] Título:Lanthanides Report Calcium Sensor in the Vestibule of Ryanodine Receptor.
[So] Source:Biophys J;112(10):2127-2137, 2017 May 23.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ca regulates ryanodine receptor's (RyR) activity through an activating and an inhibiting Ca -binding site located on the cytoplasmic side of the RyR channel. Their altered sensitivity plays an important role in the pathology of malignant hyperthermia and heart failure. We used lanthanide ions (Ln ) as probes to investigate the Ca sensors of RyR, because they specifically bind to Ca -binding proteins and they are impermeable to the channel. Eu 's and Sm 's action was tested on single RyR1 channels reconstituted into planar lipid bilayers. When the activating binding site was saturated by 50 µM Ca , Ln potently inhibited RyR's open probability (K Eu = 167 ± 5 nM and K Sm = 63 ± 3 nM), but in nominally 0 [Ca ], low [Eu ] activated the channel. These results suggest that Ln acts as an agonist of both Ca -binding sites. More importantly, the voltage-dependent characteristics of Ln 's action led to the conclusion that the activating Ca binding site is located within the electrical field of the channel (in the vestibule). This idea was tested by applying the pore blocker toxin maurocalcine on the cytoplasmic side of RyR. These experiments showed that RyR lost reactivity to changing cytosolic [Ca ] from 50 µM to 100 nM when the toxin occupied the vestibule. These results suggest that maurocalcine mechanically prevented Ca from dissociating from its binding site and support our vestibular Ca sensor-model further.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Elementos da Série dos Lantanídeos/metabolismo
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Cálcio/química
Agonistas dos Canais de Cálcio/química
Agonistas dos Canais de Cálcio/metabolismo
Agonistas dos Canais de Cálcio/farmacologia
Bloqueadores dos Canais de Cálcio/química
Bloqueadores dos Canais de Cálcio/farmacologia
Cátions/química
Cátions/metabolismo
Citosol/química
Citosol/metabolismo
Relação Dose-Resposta a Droga
Elementos da Série dos Lantanídeos/química
Bicamadas Lipídicas/química
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Microscopia Eletrônica
Microssomos/química
Microssomos/metabolismo
Modelos Moleculares
Coelhos
Canal de Liberação de Cálcio do Receptor de Rianodina/química
Retículo Sarcoplasmático/química
Retículo Sarcoplasmático/metabolismo
Venenos de Escorpião/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Calcium Channel Blockers); 0 (Cations); 0 (Lanthanoid Series Elements); 0 (Lipid Bilayers); 0 (Ryanodine Receptor Calcium Release Channel); 0 (Scorpion Venoms); 0 (maurocalcine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE


  7 / 1874 MEDLINE  
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[PMID]:28274924
[Au] Autor:Li Y; Hu H; Tian JB; Zhu MX; O'Neil RG
[Ad] Endereço:Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas.
[Ti] Título:Dynamic coupling between TRPV4 and Ca -activated SK1/3 and IK1 K channels plays a critical role in regulating the K -secretory BK channel in kidney collecting duct cells.
[So] Source:Am J Physiol Renal Physiol;312(6):F1081-F1089, 2017 Jun 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The large-conductance Ca -activated K channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca -dependent K secretion. Its activity is partially under the control of the mechanosensitive transient receptor potential vanilloid type 4 (TRPV4) Ca -permeable channel. Recently, we identified three small-/intermediate-conductance Ca -activated K channels, SK1 (KCNN1), SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca -binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca influx. The K -secreting CCD mCCDcl1 cells, which express these channels, were used to determine whether SK1/3 and IK1 are activated on TRPV4 stimulation and whether they contribute to Ca influx and activation of BK. Activation of TRPV4 (GSK1016790A) modestly depolarized the membrane potential and robustly increased intracellular Ca , [Ca ] Inhibition of both SK1/3 and IK1 by application of apamin and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), respectively, further depolarized the membrane potential and markedly suppressed the TRPV4-mediated rise in [Ca ] Application of BK inhibitor iberiotoxin after activation of TRPV4 without apamin/TRAM-34 also reduced [Ca ] and further intensified membrane depolarization, demonstrating BK involvement. However, the BK-dependent effects on [Ca ] and membrane potential were largely abolished by pretreatment with apamin and TRAM-34, identical to that observed by separately suppressing TRPV4-mediated Ca influx, demonstrating that SK1/3-IK1 channels potently contribute to TRPV4-mediated BK activation. Our data indicate a direct correlation between TRPV4-mediated Ca signal and BK activation but where early activation of SK1/3 and IK1 channels are critical to sufficiently enhanced Ca entry and [Ca ] levels required for activation of BK.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo
Túbulos Renais Coletores/metabolismo
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo
Potássio/metabolismo
Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
Canais de Cátion TRPV/metabolismo
[Mh] Termos MeSH secundário: Animais
Agonistas dos Canais de Cálcio/farmacologia
Sinalização do Cálcio
Células Cultivadas
Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores
Túbulos Renais Coletores/efeitos dos fármacos
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores
Potenciais da Membrana
Camundongos
Bloqueadores dos Canais de Potássio/farmacologia
Canais de Potássio Ativados por Cálcio de Condutância Baixa/antagonistas & inibidores
Canais de Cátion TRPV/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Intermediate-Conductance Calcium-Activated Potassium Channels); 0 (Kcnma1 protein, mouse); 0 (Kcnn1 protein, mouse); 0 (Kcnn3 protein, mouse); 0 (Kcnn4 protein, mouse); 0 (Large-Conductance Calcium-Activated Potassium Channel alpha Subunits); 0 (Potassium Channel Blockers); 0 (Small-Conductance Calcium-Activated Potassium Channels); 0 (TRPV Cation Channels); 0 (Trpv4 protein, mouse); RWP5GA015D (Potassium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00037.2017


  8 / 1874 MEDLINE  
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[PMID]:28075010
[Au] Autor:Wu SN; Chern JH; Shen S; Chen HH; Hsu YT; Lee CC; Chan MH; Lai MC; Shie FS
[Ad] Endereço:Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan.
[Ti] Título:Stimulatory actions of a novel thiourea derivative on large-conductance, calcium-activated potassium channels.
[So] Source:J Cell Physiol;232(12):3409-3421, 2017 Dec.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. The effects of compound #326 on Ca -activated K channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. In pituitary GH cells, compound #326 increased the amplitude of Ca -activated K currents (I ) with an EC value of 11.6 µM, which was reversed by verruculogen, but not tolbutamide or TRAM-34. Under inside-out configuration, a bath application of compound #326 raised the probability of large-conductance Ca -activated K (BK ) channels. The activation curve of BK channels was shifted to less depolarised potential with no modification of the gating charge of the curve; consequently, the difference of free energy was reduced in the presence of this compound. Compound #326-stimulated activity of BK channels is explained by a shortening of mean closed time, despite its inability to alter single-channel conductance. Neither delayed-rectifier nor erg-mediated K currents was modified. Compound #326 decreased the peak amplitude of voltage-gated Na current with no clear change in the overall current-voltage relationship of this current. In HEK293T cells expressing α-hSlo, compound #326 enhanced BK channels effectively. Intriguingly, the inhibitory actions of compound #326 on interleukin 1ß in lipopolysaccharide-activated microglia were significantly reversed by verruculogen, whereas BK channel inhibitors suppressed the expressions of inducible nitric oxide synthase. The BK channels could be an important target for compound #326 if similar in vivo results occur, and the multi-functionality of BK channels in modulating microglial immunity merit further investigation.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Agonistas dos Canais de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Cálcio/metabolismo
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/agonistas
Tioureia/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Ativação do Canal Iônico/efeitos dos fármacos
Cinética
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo
Lipopolissacarídeos/farmacologia
Potenciais da Membrana
Camundongos Endogâmicos BALB C
Microglia/efeitos dos fármacos
Microglia/metabolismo
Óxido Nítrico Sintase Tipo II/genética
Óxido Nítrico Sintase Tipo II/metabolismo
Neoplasias Hipofisárias/metabolismo
Ratos
Tioureia/análogos & derivados
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Calcium Channel Agonists); 0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (KCNMA1 protein, human); 0 (Kcnma1 protein, rat); 0 (Large-Conductance Calcium-Activated Potassium Channel alpha Subunits); 0 (Lipopolysaccharides); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse); GYV9AM2QAG (Thiourea); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25788


  9 / 1874 MEDLINE  
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[PMID]:27881772
[Au] Autor:Zhang H; Sun S; Wu L; Pchitskaya E; Zakharova O; Fon Tacer K; Bezprozvanny I
[Ad] Endereço:Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
[Ti] Título:Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment.
[So] Source:J Neurosci;36(47):11837-11850, 2016 Nov 23.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca channel complex in hippocampal mushroom spines. We further demonstrate that a known TRPC6 activator, hyperforin, and a novel nSOC positive modulator, NSN21778 (NSN), can stimulate activity of nSOC pathway in the spines and rescue mushroom spine loss in both presenilin and APP knock-in mouse models of AD. We further show that NSN rescues hippocampal long-term potentiation impairment in APP knock-in mouse model. We conclude that the STIM2-regulated TRPC6/Orai2 nSOC channel complex in dendritic mushroom spines is a new therapeutic target for the treatment of memory loss in aging and AD and that NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD. SIGNIFICANCE STATEMENT: Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in Alzheimer's disease (AD). This study demonstrated that Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 form stromal interaction molecule 2 (STIM2)-regulated neuronal-store-operated Ca influx (nSOC) channel complex in hippocampal synapse and the resulting Ca influx is critical for long-term maintenance of mushroom spines in hippocampal neurons. A novel nSOC-positive modulator, NSN21778 (NSN), rescues mushroom spine loss and synaptic plasticity impairment in AD mice models. The TRPC6/Orai2 nSOC channel complex is a new therapeutic target and NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Agonistas dos Canais de Cálcio/administração & dosagem
Sinalização do Cálcio/fisiologia
Espinhas Dendríticas/metabolismo
Proteína ORAI2/metabolismo
Canais de Cátion TRPC/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/metabolismo
Animais
Encéfalo
Cálcio/metabolismo
Sinalização do Cálcio/efeitos dos fármacos
Espinhas Dendríticas/efeitos dos fármacos
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
Ativação do Canal Iônico/efeitos dos fármacos
Ativação do Canal Iônico/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Proteína ORAI2/agonistas
Sinapses/efeitos dos fármacos
Potenciais Sinápticos/efeitos dos fármacos
Potenciais Sinápticos/fisiologia
Canais de Cátion TRPC/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (ORAI2 Protein); 0 (Orai2 protein, mouse); 0 (TRPC Cation Channels); 0 (Trpc6 protein, mouse); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE


  10 / 1874 MEDLINE  
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[PMID]:27662087
[Au] Autor:des Georges A; Clarke OB; Zalk R; Yuan Q; Condon KJ; Grassucci RA; Hendrickson WA; Marks AR; Frank J
[Ad] Endereço:Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
[Ti] Título:Structural Basis for Gating and Activation of RyR1.
[So] Source:Cell;167(1):145-157.e17, 2016 Sep 22.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca(2+) alone induces conformational changes in the cytoplasmic assembly ("priming"), without pore dilation. In contrast, in the presence of all three activating ligands, high-resolution reconstructions of open and closed states of RyR1 were obtained from the same sample, enabling analyses of conformational changes associated with gating. Gating involves global conformational changes in the cytosolic assembly accompanied by local changes in the transmembrane domain, which include bending of the S6 transmembrane segment and consequent pore dilation, displacement, and deformation of the S4-S5 linker and conformational changes in the pseudo-voltage-sensor domain.
[Mh] Termos MeSH primário: Agonistas dos Canais de Cálcio/química
Ativação do Canal Iônico
Contração Muscular
Canal de Liberação de Cálcio do Receptor de Rianodina/química
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Cafeína/química
Cálcio/química
Microscopia Crioeletrônica
Ligantes
Domínios Proteicos
Coelhos
Proteínas de Ligação a Tacrolimo/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Ligands); 0 (Ryanodine Receptor Calcium Release Channel); 3G6A5W338E (Caffeine); EC 5.2.1.- (Tacrolimus Binding Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170827
[Lr] Data última revisão:
170827
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160924
[St] Status:MEDLINE



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